Gompel, Jamie J. Van

Abstract Craniopharyngiomas are rare parasellar tumors, and papillary craniopharyngiomas (PCPs) represent 8 to 20% of cases. Interim analysis of retrospective data collected from the Registry of Adenomas of the Pituitary and Related Disorders (RAPID). Fourteen U.S.-based academic skull base centers between 2011 and 2023. Patients with PCPs. Demographic, imaging, surgical, and outcome variables. Ninety-nine patients with PCPs were included. The mean age was 51.8 ± 14.7, and 57.6% were male. Most tumors showed mixed cystic/solid components (67.5%), were transinfundibular (50.0%), and were treated with an endoscopic endonasal approach (74.5%), with 51.1% demonstrating gross total resection (GTR). Pituitary stalk was preserved in 51.9%. Permanent arginine vasopressin deficiency was seen in 67.1% and was associated with pituitary stalk sacrifice (p = 0.003). Cerebrospinal fluid leak was the most common nonendocrine postsurgical, 30-day complication (9.1%), reason for return to the operating room (3.1%), and reason for 90-day readmission (8.1%). Most patients (63.9%) received no adjuvant therapy; GTR was associated with decreased radiotherapy use (p = 0.0001). BRAFV600E mutation was detected in 64/69 tumors tested, although only one patient was treated with a BRAF inhibitor. A mean follow-up of 12.3 ± 14.6 months was seen for the group. RAPID consortium enabled the largest real-world clinical information dataset for PCPs. Early findings support that GTR and stalk preservation are important to outcomes. Iterative analysis and discussion of data led to the generation of a framework for future studies to fully leverage the capabilities of multicenter registries.

Abstract Despite the growing interest in network-guided neuromodulation for epilepsy, uncertainty about the safety and long-term efficacy of thalamocortical stimulation persists. Our evaluation focused on the use of a four-lead open-loop implantable pulse generator for thalamocortical network neuromodulation. We retrospectively reviewed seven patients with diverse seizure networks—poorly localized, regional, or multifocal—undergoing thalamocortical neuromodulation. Employing a four-lead system, electrodes targeted both thalamic and cortical seizure network nodes. We assessed seizure severity, life satisfaction and sleep quality on a 10-point scale, and seizure frequency was assessed via telephone interviews and chart review. Outcomes were assessed by the Wilcoxon sign-rank test at the 0.05 significance level. Seven patients with a median age at implant of 22 years (range 14–42 years) had a median disabling seizure reduction of 93% (range 50–100%, P = 0.0156), with 100% responder rate (≥50% reduction in seizure frequency) after a median of 17 months post-implantation (range 13–60). The median improvement in seizure severity was 3.5 out of 10 points (P = 0.0312), life satisfaction 4.5 points (P = 0.0312) and quality of sleep 3 points (P = 0.062). No perioperative complications occurred. Transient seizure exacerbations (n = 2) and stimulation-related sensory/motor side-effects (n = 2) quickly resolved with parameter adjustments. One patient required surgical revision due to delayed infection. Six patients had permanent electrode placement refined by intracranial EEG trial stimulation; five patients had >90% reduction in seizure frequency during trial stimulation. Thalamocortical network neuromodulation using a four-lead open-loop system is safe and associated with significant improvements in seizure control and patient quality of life. Trial stimulation during intracranial EEG shows promise for enhancing seizure network engagement and parameter optimization but requires further study. Prospective controlled trials are needed to further characterize and validate the efficacy and side-effect profile of thalamocortical network neuromodulation for epilepsy.

OBJECTIVE Patients with growth hormone (GH)–secreting pituitary adenomas (PAs) experience various symptoms and comorbidities, which can ultimately lead to increased mortality. This study aimed to develop and validate a machine learning (ML) model for predicting long-term outcomes in patients with GH-secreting PAs following endonasal transsphenoidal surgery (ETS). METHODS The authors conducted a retrospective three-institution cohort study that included patients with GH-secreting PAs treated with ETS between 2013 and 2023. Clinical, radiological, and biochemical data were collected. The main outcome of interest was the intervention-free rate (IFR) after primary ETS. Supervised ML algorithms, including decision trees and random forests, were developed to predict the IFR. Model performance was evaluated using area under the receiver operating characteristic curve (AUROC) and Shapley Additive Explanations (SHAP) values. RESULTS The median follow-up for 100 patients with GH-secreting PAs (53% female) was 64 months (range 1–130 months). Additional intervention for persistent or recurrent acromegaly was required in 32% of patients. Following primary ETS alone, the 3-year IFR was 70% and the 5-year IFR was 67%. Multiple ML models were developed and evaluated using AUROCs. The decision tree analysis achieved an accuracy of 81% and emphasized the importance of both gross-total resection (GTR) and patient age in determining the long-term IFR. To better understand the factors that contributed to model performance, SHAP analysis was applied to the best-performing model. The SHAP dependence plots showed that key factors associated with a longer IFR included tumor size < 9 mm, GTR, patient age > 65 years, and Knosp grade 0. CONCLUSIONS This ML model offers a more nuanced and potentially more accurate approach to identify patients more likely to develop recurrent or persistent acromegaly following primary ETS and require additional treatment. Following external validation, this ML model could improve personalized treatment planning and follow-up strategies and enhance patient care and resource allocation in clinical practice.

Summary: Epilepsy neuromodulation treatment failure is a significant challenge, with multiple possible causes. The responsive neurostimulation (RNS) system delivers stimulation from a single current source, and the relative flow of the electrical current through each stimulating contact is inversely proportional to the relative impedance of each contact. Current shunting through low-impedance contacts (i.e., intraventricular contacts) can divert therapy away from the intended targets and may be a cause of treatment failure. We present a case of a patient with bitemporal epilepsy and bitemporal encephaloceles, with poor response to bilateral mesial temporal RNS, who completed stereotactic EEG (sEEG) monitoring to investigate the possible causes of treatment failure. The sEEG was safely completed without damaging the RNS device. The sEEG recorded independent bitemporal interictal epileptiform discharges and seizures, which did not arise from sampled encephalocele regions. The sEEG-recorded RNS stimulation artifact was reduced in the left mesial temporal region relative to the right, which suggested potential current shunting through the right-sided contacts. Impedance measurements confirmed several low-impedance contacts from the right lead, with associated intraventricular position on imaging. At last follow up, 161 days after replacement of the right lead, the patient experienced an additional 58% reduction in seizure burden. Effective therapy delivery by single-current-source neurostimulation systems, such as RNS, critically depends on relative electrode impedances. Current shunting through low-impedance contacts is an underappreciated potential cause of treatment failure. Routine impedance assessments and individualized stimulation programs are recommended to avoid unintended current diversion. Concurrent sEEG monitoring and active RNS are feasible and can characterize stimulation effects.

OBJECTIVE Calcium phosphate cement (CPC) use has been previously described as a strategy to reduce the rates of pseudomeningocele and CSF leakage following skull base surgery. The authors aimed to present their institutional experience with CPC in retrosigmoid craniotomy and perform a systematic review of the literature to determine the effectiveness of CPC in reducing postoperative complications, including pseudomeningocele and craniotomy-site CSF leakage. METHODS A retrospective single-institution cohort study of patients who underwent retrosigmoid craniotomy with and without CPC cranioplasty from January 2017 to April 2024 was performed. A systematic literature review and meta-analysis of CPC use in retrosigmoid craniotomy was also performed. RESULTS Of 336 patients who underwent retrosigmoid craniotomy, 193 (57%) were female and the median age at surgery was 55 years (range 18–81 years). The median follow-up duration was 23 months (range 3–80 months). CPC was used to seal the edge of the craniotomy in 66 patients (20%). Among all patients, 50 (15%) experienced a postoperative complication, and 28 (8%) were wound-specific complications. Patients in the non-CPC group experienced significantly more postoperative wound-specific complications than those in the CPC group (10% vs 0%, p = 0.002). Specifically, pseudomeningocele occurred in 0 patients (0%) in the CPC group compared with 24 patients (9%) in the non-CPC group (p = 0.006), which progressed to CSF leaks at the craniotomy site in 6 patients (p = 0.60). Additionally, no patients (0%) in the CPC group experienced wound infection, dehiscence, or breakdown compared with 10 patients (4%) in the non-CPC group (p = 0.22). Five patients (8%) in the CPC group reported prolonged mild incisional pain at the craniotomy site, and there were no instances of major complications related to the CPC. In the meta-analysis, 10 studies met the inclusion criteria, yielding a total of 2166 patients (including the current study), 1101 of whom received CPC. In the pooled analysis, CPC was significantly associated with lower risk of CSF leakage at the craniotomy site (OR 0.23, 95% CI 0.13–0.42; p < 0.01) and lower risk of infection (OR 0.17, 95% CI 0.08–0.38; p < 0.01). CONCLUSIONS CPC use in retrosigmoid craniotomies could be a safe and effective strategy to reduce the incidence of pseudomeningocele and craniotomy-site CSF leakage, leading to lower rates of wound-related complications and infection.

BACKGROUND: Surgical intervention remains an important option in the management of vestibular schwannoma (VSs). Development of a systematic approach to choose the most appropriate route for this intervention, based on existing published evidence, is an important goal. OBJECTIVE: To review the literature published since the 2018 Congress of Neurological Surgeons Guideline on surgical intervention for patients with sporadic VSs and use this information to update that set of recommendations. METHODS: The literature in the PubMed and MEDLINE databases from January 2015 through May 20, 2022, was searched for manuscripts pertaining to surgical intervention for VSs. Those manuscripts meeting inclusion criteria were then analyzed for creation of recommendations in response to a set of updated questions. RESULTS: The resultant findings included a considerable amount of data that did not alter the recommendations form the 2018 publication on this topic. Thus, recommendations stating hearing preservation surgery through the middle fossa or retrosigmoid approach may be considered in individuals with good preoperative hearing as an alternative to simple observation remain. In addition, if microsurgical resection is necessary after stereotactic radiosurgery, it is recommended that patients be counseled that there is an increased likelihood of a subtotal resection and decreased facial nerve function. In some questions, insufficient data were present to create an answer and that is stated. CONCLUSION: This guideline demonstrates surgical intervention for VSs and represents a range of options, and the choice of the intervention depends on the specific aspects of the lesion and the individual that harbors them. Objective refinement of those choices will require thoughtful research design by investigations that wish to address those items for which we still have insufficient information. The full guideline can be seen online at https://www.cns.org/guidelines/treatment-adults-vestibular-schwannoma/7-surgical-resection-treatment-of-patients-with-ve-2

BACKGROUND: Imaging is a critical aspect of vestibular schwannoma (VS) management, influencing essentially every aspect of care including diagnosis, surveillance, treatment decision making, and follow-up after either resection or stereotactic radiosurgery. Despite this, treatment protocols are heterogeneous, and frequently based on historical practices, or low-quality evidence. OBJECTIVE: To update evidence-based guidelines for the use of imaging in the clinical management of patients with VS published by the Congress of Neurological Surgeons in 2018. METHODS: Systematic review of the literature published from 1/1/2015 to 5/20/2022 regarding imaging protocols for VS management. Salient questions were identified by a writing group of diverse individuals with topic-specific expertise. Questions were validated by the Congress of Neurological Surgeons Guidelines Committee. Following systematic review, literature tables and summary statements pertinent to the study questions were generated by the writing group, which underwent subsequent evaluation and revision by the task force before formalization. RESULTS: Seven questions were formulated; adequate literature was identified to formulate updated recommendations for 6 of these. Search strategy identified 1143 unique records, of which 109 underwent full-text review, and 57 were included in this study. Most studies provided level III evidence, with rare level II studies noted, yielding level III recommendations. CONCLUSION: The current evidence base for imaging protocols in VS clinical management is broad, diverse, low certainty, and low quality. This in part reflects a heterogeneous disease, although variability in treatment philosophies may also influence local decision making. Key areas for future study include the clinical utility of advanced imaging techniques and head-to-head comparisons of imaging protocols for patients in common initial VS management pathways (eg, observation, resection, or stereotactic radiosurgery). The full guideline can be seen online at https://www.cns.org/guidelines/treatment-adults-vestibular-schwannoma/5-role-of-imaging-in-management-of-patients-with-v

BACKGROUND: Given the increasing prevalence and shifting disease demographic of vestibular schwannoma toward smaller tumors in people with less advanced symptoms, increasing emphasis has been placed on functional hearing preservation. OBJECTIVE: To provide an update to the 2018 CNS Guideline on hearing preservation outcomes in patients with sporadic vestibular schwannoma. METHODS: Systematic review and clinical practice guideline summarizing data pertaining to hearing preservation outcomes within the first 10 years after contemporary stereotactic radiation, microsurgery, or observation with serial imaging. The analysis incorporates studies included in the 2018 guideline and additional literature published up to May 20, 2022, providing a comprehensive up-to-date review of published clinical outcome data over time. RESULTS: Pooled estimated rates of serviceable hearing preservation are presented for observation, radiosurgery, and microsurgery for adults with sporadic vestibular schwannoma who have documented serviceable hearing in the ipsilateral ear at the time of diagnosis. Overall estimated rates of maintaining serviceable hearing are 78% at 2 years, 59% at 5 years, and 47% at 10 years during observation; 71% at 2 years, 59% at 5 years, and 38% at 10 years after radiosurgery; and 48% at 2 years, 40% at 5 years, and 32% at 10 years after microsurgery. In addition, features portending hearing outcome among management modalities are reported to guide accurate patient counseling. CONCLUSION: Regardless of treatment modality, fewer than half of patients with sporadic vestibular schwannoma who present with serviceable hearing will maintain useful hearing by 10 years. Across all studies, microsurgery and radiosurgery seem to accelerate this decline over the natural history, although further research is needed given limitations of available evidence. The full guideline can be seen online at https://www.cns.org/guidelines/treatment-adults-vestibular-schwannoma/4-hearing-preservation-outcomes-in-patients-with-s

OBJECTIVE Reports of surgical outcomes for Cushing’s disease are mostly limited to single-center experiences by expert surgeons. Therefore, no generalizable surgical outcome metrics for endoscopic endonasal Cushing’s disease surgery are available for practitioners to guide quality-improvement efforts. This is potentially problematic, given the high morbidity and excess mortality observed in patients who do not achieve remission. This study proposes a bundle of evidence-based metrics for low-risk patients with Cushing’s disease, for whom optimal outcomes would be expected, that focus on the cost efficiency of care and surgical outcomes from multicenter collaboration of US pituitary centers. METHODS The steering committee of the Registry of Adenomas of the Pituitary and Related Disorders (RAPID) consortium proposed the metrics based on available data from 12 US pituitary centers. A benchmarking population of low-risk patients undergoing first-time surgery was identified. Patient characteristics and outcomes were aggregated and analyzed by a data coordinating center. Metrics were reported using 2 approaches. RESULTS A total of 431 patients from 12 centers who underwent primary endoscopic transsphenoidal surgery from January 1, 2006, to December 31, 2022, were included. There were 227 patients in the low-risk cohort (age < 70 years, BMI < 50, microadenoma, and Knosp grade 0–2). For the cost-efficiency metrics, the mean (SD) length of stay was 3.8 (4.8) midnights, and the percentage of patients readmitted was 11.1%. The rate of disposition to a skilled nursing facility was 2.2%. For surgical outcomes, the rate of postoperative CSF leakage was 1.3%, and the rate of 1-year sustained surgical remission was 81.2%. The rates of permanent and temporary arginine vasopressin deficiencies were 1.8% and 11.9%, respectively. The 75th percentile performance by center was 3.0 midnights for length of stay, 6.3% for 90-day unplanned readmission, < 1% for disposition to a skilled nursing facility, < 1% for CSF leakage, and 92.2% for 1-year sustained remission. The 75th percentile was < 1% for both permanent and temporary arginine vasopressin deficiencies. CONCLUSIONS An evidence-based bundle of metrics in a Cushing’s disease patient population at low risk who underwent first-time endoscopic pituitary surgery is proposed. Surgeons can use these metrics to assess and improve the quality of their clinical pathways.